Sugar-based amphiphilic nanoparticles arrest atherosclerosis in vivo
Open accessAbstract
Significance: Lipid-rich plaques in major blood vessels recruit macrophages that further exacerbate the lipid burden and risk of heart attacks or stroke. A local approach to prevent plaque growth has yet to be successfully deployed. In this study, we examine how synthetic ligands counteract macrophage atherogenesis and de-escalate plaque burden. Using a library of sugar-based amphiphilic core-shell layered nanoparticles, we demonstrate the design principles necessary to prevent oxidized lipid uptake and suppress scavenger receptor expression in macrophages, switching them to an “atheroprotective” phenotype. When administered in vivo, nanoparticles were retained at atherosclerotic lesions, where they mitigated cholesterol clefts, inflammation, and artery occlusion. Thus, synthetic nanomedicines could be used to potentially treat acute coronary syndrome, a major unmet need in cardiovascular diseases.
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Confocal microscopy suggests localization of NPs around necrotic core of plaques.
“Confocal microscopy suggests the localization of NPs around the necrotic core of plaques (Fig. 5d).”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [154]
NPs accumulated at highest concentration in aortic arch and carotid branch points of ApoE−/− mice.
“NPs were found to accumulate at the highest concentration in these aortic areas, as confirmed by fluorescence imaging and corresponding quantitative data (Fig. 5b, c).”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [154]
Artery occlusion was significantly reduced after M12PEG treatment.
“Morphologically, artery occlusion was found to be significantly reduced after treatment.”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [154]
Atherosclerotic lesion-specific delivery of NPs was reported in aortas of ApoE−/− mice.
“Furthermore, atherosclerotic lesion-specific delivery of NPs was reported in the aortas of ApoE−/− mice.”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [154]
M12PEG downregulated scavenger receptors MSR1 and CD36, resulting in minimal lipid accumulation in ApoE−/− mouse model.
“Sugar-based amphiphilic macromolecules (AMs) fabricated into serum-stable NPs (M12PEG) downregulated the scavenger receptors MSR1 and CD36, resulting in minimal lipid accumulation in an atherosclerosis-prone apolipoprotein E-deficient (ApoE−/−) cardiovascular disease mouse model.154”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [154]
M12PEG mitigated lipid accumulation, inflammation, and neointimal hyperplasia in atherosclerotic disease.
“M12PEG was also able to mitigate lipid accumulation (Oil Red O), inflammation (COX-2) and neointimal hyperplasia (smooth muscle cell, α-actin), demonstrating its efficacy in atherosclerotic disease (Fig. 5e–g).154”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [154]
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- Authors
- Lewis, D. R., Petersen, L. K., York, A. W., Zablocki, K. R., Joseph, L. B., Kholodovych, V., Prud’homme, R. K., Uhrich, K. E., & Moghe, P. V.
- Affiliations
- Department of Chemical & Biochemical Engineering,
- Department of Biomedical Engineering,
- Department of Pharmacology,
- Rutgers, The State University of New Jersey (US)
- Princeton University (US)
- Department of Chemistry and Chemical Biology, and
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2015-02-17
- Volume
- 112
- Issue
- 9
- Pages
- 2693-2698
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4352838
- OpenAlex
- W2008371536
- Cited by
- 111
- References
- 35
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 11 · 2023: 7 · 2022: 11 · 2021: 13 · 2020: 9 · 2019: 12 · 2018: 12 · 2017: 11 · 2016: 12 · 2015: 8
- FWCI
- 7.07
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- HHS | NIH | National Heart, Lung, and Blood Institute (R01HL107913, R21HL93753)
- HHS | NIH | National Institute of Biomedical Imaging and Bioengineering (EB005583)
- HHS | NIH | National Institute of General Medical Sciences (T32GM008339)
- HHS | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (U54AR055073)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- atherosclerosis, core-shell nanoparticles, macrophages, scavenger receptors, MSR1, CD36, foam cells, atherosclerotic plaque, intimal hyperplasia, nanomedicine, hyperlipidemia, metabolic syndrome
- MeSH terms
- Animals, Carbohydrates, Humans, Hyperplasia, Lipids, Macrophages, Oxidation-Reduction, Mice, Knockout, CD36 Antigens, Atherosclerosis, Scavenger Receptors, Class A, Mice, Nanoparticles, Plaque, Atherosclerotic, Neointima
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